Paroxysmal Nocturnal HemoglobinuriaIn: The Asia Pacific Clinical Trial Landscape

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition that affects the ability of hematopoietic stem cells and their cellular offspring to bind specific proteins to the cell surface. Loss of the complement inhibitors CD55 and CD59 on the surface of red blood cells (RBC) causes chronic and/ or paroxysmal intravascular hemolysis, which increases the risk of thrombosis. Additionally, a small minority of patients may have clinically severe myelodysplastic syndrome or aplastic anemia, hypocellular or dysplastic bone marrow, or both.(1) Periodic instances of hemoglobinuria (the presence of hemoglobin in the urine) are caused by the red blood cells’ complement-mediated cell death. The formation of PNH requires both a phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) gene mutation that affects one or more hematopoietic stem cells, producing defective “PNH” blood cells, and a mechanism that promotes the proliferation and expansion of these defective stem cells. (2) Aplastic anaemia patients have a 15% to 25% chance of developing clinical PNH. If PNH patients are not treated, their 10-year mortality rate is 29%. (3)